Synthesis of Valproic acid derivatives and their evaluation for anticonvulsant activity

Valproic acid is simple branched chain carboxylic acid used in epilepsy. Valproic acid derivatives like acid chloride and amide were prepared by the reaction of valproic acid with thionyl chloride and ammonia. These acid chloride derivatives were reacted with hydrazine hydrate to give the corresponding hydrazides. These hydrazides were reacted with formaldehyde and different secondary amines to give substituted derivatives. The structures of the newly synthesized compounds were elucidated on the basis of analytical and spectral data. The compounds synthesized were then screened for anticonvulsant activity. Various studies were conducted on development of various prodrugs and derivatives of valproic acid. The present study showed that all synthesized amide derivatives (RDG1...RDG8) except RDG2 were more active than sodium valproate in chemical induced model as well as MES model. Amongst all the derivatives RDG3 was found to be more effective than even valpromide.